CAR T cells: driving the road from the laboratory to the clinic

EJ Cheadle, H Gornall, V Baldan… - Immunological …, 2014 - Wiley Online Library
EJ Cheadle, H Gornall, V Baldan, V Hanson, RE Hawkins, DE Gilham
Immunological reviews, 2014Wiley Online Library
Blockbuster antibody therapies have catapulted immune‐based approaches to treat cancer
into the consciousness of mainstay clinical research. On the back of this, other emerging
immune‐based therapies are providing great promise. T‐cell therapy is one such area
where recent trials using T cells genetically modified to express an antibody‐based chimeric
antigen receptor (CAR) targeted against the CD 19 antigen have demonstrated impressive
responses when adoptively transferred to patients with advanced chronic lymphocytic …
Summary
Blockbuster antibody therapies have catapulted immune‐based approaches to treat cancer into the consciousness of mainstay clinical research. On the back of this, other emerging immune‐based therapies are providing great promise. T‐cell therapy is one such area where recent trials using T cells genetically modified to express an antibody‐based chimeric antigen receptor (CAR) targeted against the CD19 antigen have demonstrated impressive responses when adoptively transferred to patients with advanced chronic lymphocytic leukemia. The general concept of the CAR T cell was devised some 20 years ago. In this relatively short period of time, the technology to redirect T‐cell function has moved at pace facilitating clinical translation; however, many questions remain with respect to developing the approach to improve CAR T‐cell therapeutic activity and also to broaden the range of tumors that can be effectively targeted by this approach. This review highlights some of the underlying principles and compromises of CAR T‐cell technology using the CD19‐targeted CAR as a paradigm and discusses some of the issues that relate to targeting solid tumors with CAR T cells.
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